Carboxylative Methodologies via Photoredox Catalysis

Abstract

Carboxylic acids are crucial intermediates in pharmaceutical drug development, and methods providing access to them are therefore significant. Photoredox chemistry has also influenced the creation of new carboxylation techniques, which is the focus of the present thesis. The thesis details the development of three distinct methodologies utilizing C1 molecules, specifically carbon dioxide or formic acid salts, for the catalytic formation of carboxylic acids in organic compounds. These approaches all involve photoredox chemistry and collectively contribute to the shift toward greener methods of producing carboxylic acids. The reactions exhibit good functional group tolerance along with mild reaction conditions. Two of the three methods presented can be applied as labeling techniques, enabling the incorporation of heavier isotopes of carbon into organic molecules, an essential aspect in pharmaceutical drug development. The first reaction described involves a multicomponent coupling of inexpensive and readily available starting materials, resulting in a structurally complex carboxylic acid entity in one sequence. The following two methodologies demonstrate the development of innovative methods for catalytic access to secondary carboxylic acids from the corresponding unactivated secondary alkyl bromides. This transformation, which had not been reported prior to the work done in this thesis, thus addresses a previously unmet challenge within the synthetic chemistry community.